Test of therapies on mini-tumors of head and neck cancer

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Healthy against tumor Tissue and OrganoidsTumor-cultured organoids and healthy tissue of a patient with head and neck cancer. Both the original tissue and the organoids are colored with hematoxylin (purple) and eosin (pink), a standard coloration used in diagnostics. Tumor organoids appear to be different from organoids grown from healthy tissue and also retain the characteristics of the original tumor tissue.Credit: Else Driehuis, © Hubrecht Institute

Head and neck cancer is a type of aggressive cancer that often grows back, despite patients undergoing hard treatments. Researchers of Hubrecht Institute (KNAW) e UMC Utrecht managed to grow mini-tumors (or organoids) of head and neck tumors, which can be kept alive in the Petri dish for a long time. Else Driehuis, researcher at the Hubrecht Institute: "These mini-tumors can be used to better understand this complex disease, and in addition, organoids allow us to test both new and existing therapies in the laboratory, without burdening the patient."

Head and neck cancer is among the 10 most common cancers in the world. In the Netherlands, more than 3,000 people are diagnosed with this disease every year. Despite heavy treatments that include surgery, radiotherapy and chemotherapy, this type of aggressive cancer grows within two years in 40-60% of patients. This results in problems speaking and swallowing and can have great consequences for the patient's physical appearance. "The treatment of head and neck cancer is hard," according to the medical oncologist Lot Devriese (UMC Utrecht). Often, a combination of therapies that can lead to serious side effects is needed to treat the disease. Therefore, there is an urgent need to make treatments more effective and reduce side effects ".

Surgery

Researchers working in the group of Hans Clevers (Hubrecht Institute) and doctors and researchers at the UCTR in Utrecht have now shown that organoids can be grown by so-called squamous cell carcinomas of the head and neck (HNSCC). These mini-organs are derived from patient material, for example obtained from the tumor mass removed during surgery. The organoid tumors of 30 patients diagnosed with head and neck cancer have been cultured for over a year. "This is the first time researchers have been successful in the cultivation of organoids derived from head and neck cancers on this scale," says pathologist Stefan Willems (UMC Utrecht). "This technique allows us to multiply a patient's cancer cells in the laboratory and will contribute to our understanding of head and neck cancer."

Radiotherapy

After growing the mini-tumors, they were exposed to chemotherapy currently given to patients with head and neck cancer. Since radiotherapy is also a common component of the treatment of these patients, organoids have also been exposed to radiotherapy. Their response to radiotherapy was known for seven patients. After exposure to this therapy, organoids derived from these patients behaved in the same way as tumors in these patients. "We have now begun a study in which we will include more patients to see if organoids can actually predict patients' response to therapy," says Else Driehuis (Hubrecht Institute). "At the moment, many patients are exposed to chemotherapy doses, while some of them in hindsight did not benefit from this therapy. In the laboratory, we can test many different drugs at the same time to see how the patient's tumor organs respond to them. Potentially, these tests can help us choose the right therapy for each individual patient. "

Forecast of patient response

The researchers also exposed the mini-tumors to a series of new drugs, the so-called "targeted therapies". As the name suggests, these drugs have a very targeted effect and therefore cause less serious side effects than conventional chemotherapy. The downside: they only work for a subset of patients who carry specific alterations in the DNA of their tumor. "For some of these drugs, it has been difficult to predict which patients will benefit from the treatment, but unfortunately this has limited the success of these promising therapies so far," says Driehuis. "In our study, we observed that each of the drugs we tested was effective in at least one patient's organoids. Further research will tell us if organoid-tumors can also predict the patient's response to these therapies."

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